Gardasil
Encyclopedia
Gardasil also known as Gardisil or Silgard, is a vaccine
for use in the prevention of certain types of human papillomavirus
(HPV), specifically HPV
types 6, 11, 16 and 18. HPV types 16 and 18 cause an estimated 70% of cervical cancer
s, and are responsible for most HPV-induced anal
, vulvar
, vaginal
, and penile cancer cases. HPV types 6 and 11 cause an estimated 90% of genital warts cases.
Gardasil has been used in prevention of two types of HPV infections, associated with approximately 70% of HPV cases. It does not treat existing infection. Therefore, to be effective it must be given before HPV infection occurs. The HPV strains that Gardasil protects against are sexually transmitted.
It was approved in the US on June 8, 2006 by the U.S. Food and Drug Administration (FDA). The FDA recommends vaccination before adolescence and potential sexual activity.
, Georgetown University
, and the US National Cancer Institute
(NCI). In 1991, Australian investigators at The University of Queensland found a way to form non-infectious virus-like particles (VLP), which could also strongly activate the immune system. However, these VLPs assembled poorly and did not have the same structure as infectious HPV. In 1993, a laboratory at the US National Cancer Institute was able to generate HPV16 VLPs that were morphologically correct. These VLPs were the basis for the HPV16 component of the Gardasil vaccine. Upon commercialization of the vaccine, controversy involving intellectual property arose between the various groups that played a role in developing the vaccine.
group and one vaccination group. Over 12,000 women aged 16–26 from thirteen countries participated in the study. Each woman was injected with either Gardasil or a placebo on day 1, month 2, and month 6. In total, 6,082 women were given Gardasil and 6,075 received the placebo. Subjects in the vaccine group had a significantly lower occurrence of high-grade cervical intraepithelial neoplasia related to HPV-16 or HPV-18 than did those in the placebo group. On February 27, 2006, the independent Data and Safety Monitoring Board recommended the clinical trials be terminated on ethical grounds, so that young women on placebo could receive Gardasil. Merck tested the vaccine in several hundred 11- and 12-year-old girls.
Since Gardasil will not block infection with all of the HPV types that can cause cervical cancer, the vaccine should not be considered a substitute for routine pap smear
s.
Fewer HPV infections mean fewer complications from the virus and less time and money spent on the detection, work-up, and treatment of cervical cancer and its precursor, cervical dysplasia. It prevents infertility caused by cervical biopsies and reduces the severe respiratory problems of children who are infected by HPV from their mothers.
In addition, protection against HPV 6 and HPV 11 is expected to eliminate 90% of the cases of genital warts. Gardasil also protects against vulvar
and vaginal cancer
s caused by HPV types 16 and 18.
In December 2010, Gardasil was approved by the FDA for prevention of anal cancer and associated precancerous lesions due to human papillomavirus (HPV) types 6, 11, 16, and 18 in people ages 9 through 26 years.
HPV infections, especially HPV 16, contribute to some head and neck cancer
(HPV is found in an estimated 26-35% of head and neck squamous cell carcinoma). In principle, HPV vaccines may help reduce incidence of such cancers caused by HPV, but this has not been demonstrated.
Merck was denied FDA approval to market Gardasil to women aged 27 to 45. Although it was found to be safe and effective in the prevention of genital warts, it was not effective in the prevention of cervical cancer in that age group.
, and some potentially precancerous lesions caused by some HPV types. An ongoing study of 4,065 males demonstrated the efficacy of Gardasil in males who did not have HPV infection prior to vaccination. The vaccination is expected to protect against penile cancer and anal cancer
caused by included HPV types, and research in this area is still underway.
In December 2008, Merck asked the U.S. Food and Drug Administration (FDA) for permission to market the vaccine in the United States for males between ages 9 to 26, and the FDA approved the request on October 16, 2009. In the UK, HPV vaccines are already licensed for males aged 9 to 15 and for females aged 9 to 26.
Gardasil is in particular demand among gay men
, who are at significantly increased risk for genital warts and anal cancer caused by HPV.
A 2005 study in San Francisco, California found that 95% of HIV
-infected gay men also had anal HPV infection, of which 50% had precancerous HPV-caused lesions.
Type 16 is also associated with oropharyngeal squamous-cell carcinoma, a form of throat cancer.
protein, L1, can spontaneously self-assemble into virus-like particles (VLPs) that resemble authentic HPV virions. Gardasil contains recombinant
VLPs assembled from the L1 proteins of HPV types 6, 11, 16 and 18. Since VLPs lack the viral DNA
, they cannot induce cancer. They do, however, trigger an antibody
response that protects vaccine recipients from becoming infected with the HPV types represented in the vaccine. The L1 proteins are produced by separate fermentation
s in recombinant Saccharomyces cerevisiae
and self-assembled into VLPs.
says, "Studies have shown that both Gardasil and Cervarix prevent nearly 100 percent of the precancerous cervical cell changes caused by the types of HPV targeted by the vaccine for up to 4 years after vaccination among women who were not infected at the time of vaccination."
Gardasil has been shown to be partially effective (approximately 38%) in preventing cervical cancer caused by ten other high-risk HPV types.
(FDA) and the Centers for Disease Control and Prevention
(CDC) consider the vaccine to be safe. It does not contain mercury
, thiomersal
or live virus or dead virus, only virus-like particles, which cannot reproduce in the human body.
The FDA and the CDC say that the vaccine has only minor side effects, such as soreness around the injection area. Fainting is more common among adolescents receiving the Gardasil vaccine than in other kinds of vaccinations. Patients should remain seated for 15 minutes after they receive the HPV vaccine. There have been reports that the shot is more painful than other common vaccines, and the manufacturer Merck partly attributes this to the virus-like particles within the vaccine. General side effects of the shot may include joint and muscle pain, fatigue, physical weakness and general malaise.
An update on adverse events was published by the Journal of the American Medical Association
and looked at data from the Vaccine Adverse Event Reporting System
(VAERS), covering 12,424 reported adverse events after about 23 million doses of vaccine between June 2006 and December 2008. Most adverse effects were minor and not greater than background rates compared with other vaccines, the exception being higher rates for syncope
and venous thromboembolic events. Venous thromboembolic events were noted in 56 reports at a rate of 0.2 cases per 100,000 doses distributed and included 19 cases of pulmonary embolism, four of which were fatal. Overall, 772 events (6.2% of the total number of adverse events, but only 0.003% of the total number of doses) were described as serious and included 32 deaths (1 per 1,000,000 doses).
Other adverse events include local site reactions (7.5 cases per 100,000 doses distributed), headaches (4.1 cases per 100,000 doses distributed), hypersensitivity reactions (3.1 cases per 100,000 doses distributed), and urticaria
(hives) (2.6 cases per 100,000 doses distributed).
The FDA and the CDC said that with millions of vaccinations "by chance alone some serious adverse effects and deaths" will occur in the time period following vaccination, but have nothing to do with the vaccine. More than 20 women who received the Gardasil vaccine have died, but these deaths have not been causally connected to the shot. Where information has been available, the cause of death was explained by other factors. Likewise, a small number of cases of Guillain-Barré Syndrome
(GBS) have been reported following vaccination with Gardasil, there is no evidence linking GBS to the vaccine. It is unknown why a person contracts GBS, or what initiates the disease.
The FDA and the CDC monitor events to see if there are patterns, or more serious events than would be expected from chance alone. The majority (68%) of side effects data were reported by the manufacturer, but in about 90% of the manufacturer reported events, no follow-up information was given that would be useful to investigate the event further. In February 2009, the Spanish ministry of health suspended use of one batch of Gardasil after health authorities in the Valencia region reported that two girls had become ill after receiving the injection. Merck has stated that there was no evidence Gardasil was responsible for the two illnesses.
writes:
Whether the effects are temporary or life-long, widespread vaccination could have a substantial public health impact. 270,000 women died of cervical cancer worldwide in 2002. Acting FDA Administrator Dr. Andrew von Eschenbach
said the
vaccine will have "a dramatic effect" on the health of women around the world. Even in the United States, where screening programs are routine, the National Cancer Institute
estimated that 9,700 women would develop cervical cancer in 2006, and 3,700 would die.
Merck and CSL Limited
are expected to market Gardasil as a cancer vaccine, rather than an STD
vaccine. It remains unclear how widespread the use of the three-shot series will be, in part because of its $360 list price ($120 each for three shots).
Since both men and women are carriers of HPV, vaccination of males could provide greater herd immunity
.
Studies using different pharmacoeconomic models predict that vaccinating young women with Gardasil in combination with screening programs may be more cost effective than screening alone. These results have been important in decisions by many countries to start vaccination programs. For example, the Canadian government approved $300 million to buy the HPV vaccine in 2008 after deciding from studies that the vaccine would be cost-effective especially by immunizing young women. Marc Steben, an investigator for the vaccine, wrote that the financial burden of HPV related cancers on the Canadian people was already $300 million per year in 2005, so the vaccine could reduce this burden and be cost-effective.
Since penile and anal cancers are much less common than cervical cancer, HPV vaccination of young men is likely to be much less cost-effective than for young women.
Diane Harper, one of the lead researchers for Gardasil, has called for more complete warnings for parents and questions its risk-versus-benefit profile because it is not yet known how long the vaccine will be effective once administered. The August 2009 issue of the Journal of the American Medical Association
had an article reiterating the safety of Gardasil and another questioning the way it was presented to doctors and parents.
In an address at the 4th International Public Conference on Vaccination sponsored by the anti-vaccination group the National Vaccine Information Center
in October 2009, Dr. Diane Harper stated that in countries where Pap smear screening is common, it will take vaccination of a large proportion of women in order to further reduce cervical cancer rates. She also stated that no efficacy trials for children under 15 have been performed.
Objections from doctors and parents groups were due to the vaccine protecting against a sexually transmitted disease, human papilloma virus, which causes cervical cancer. They cited that vaccines mandated are typically for diseases spread through casual contact, such as measles and mumps.
On February 20, 2007, Merck announced its immediate suspension of this campaign, which had been funded through a third party.
The governor of Texas, Rick Perry
, issued an executive order adding Gardasil to the state's required vaccination list which was later overturned by the Texas legislature. Perry has also allowed parents to more easily opt-out of the program. Through lobbying efforts, Merck has suggested that governments make vaccination with Gardasil mandatory for school attendance, which has upset some conservative groups and libertarian groups. Conservative groups, including the Family Research Council
(FRC), have expressed fear that vaccination with Gardasil might give girls a false sense of security regarding sex and lead to promiscuity.
During the Republican Party presidential debate
on September 12, 2011, candidates Congressman Ron Paul
and Representative Michele Bachmann
criticized fellow candidate Governor Rick Perry
for his executive order. The following day, on the NBC Today Show Bachmann said “I will tell you that I had a mother last night come up to me here in Tampa, Fla., after the debate and tell me that her little daughter took that vaccine, that injection, and she suffered from mental retardation
thereafter". In response, Merck rejected claims that Gardasil causes mental retardation and stated this side effect has never been reported for this vaccine. The comment may have resulted from confusion over the thimerosal controversy, in which similar claims have been made for other vaccines, but Gardasil does not contain thimerosal.
HPV vaccine
The human papilloma virus vaccine prevents infection with certain species of human papillomavirus associated with the development of cervical cancer, genital warts, and some less common cancers...
for use in the prevention of certain types of human papillomavirus
Human papillomavirus
Human papillomavirus is a member of the papillomavirus family of viruses that is capable of infecting humans. Like all papillomaviruses, HPVs establish productive infections only in keratinocytes of the skin or mucous membranes...
(HPV), specifically HPV
Human papillomavirus
Human papillomavirus is a member of the papillomavirus family of viruses that is capable of infecting humans. Like all papillomaviruses, HPVs establish productive infections only in keratinocytes of the skin or mucous membranes...
types 6, 11, 16 and 18. HPV types 16 and 18 cause an estimated 70% of cervical cancer
Cervical cancer
Cervical cancer is malignant neoplasm of the cervix uteri or cervical area. One of the most common symptoms is abnormal vaginal bleeding, but in some cases there may be no obvious symptoms until the cancer is in its advanced stages...
s, and are responsible for most HPV-induced anal
Anal cancer
Anal cancer is a type of cancer which arises from the anus, the distal orifice of the gastrointestinal tract. It is a distinct entity from the more common colorectal cancer. The etiology, risk factors, clinical progression, staging, and treatment are all different. Anal cancer is typically a...
, vulvar
Vulvar cancer
Vulvar cancer, a malignant invasive growth in the vulva, accounts for about 4 % of all gynecological cancers and typically affects women in later life. It is estimated that in the United States in 2006 about 3,740 new cases will be diagnosed and about 880 women will die as a result of vulvar cancer...
, vaginal
Vaginal cancer
Vaginal cancer is any type of cancer that forms in the tissues of the vagina. Primary vaginal cancer is rare in the general population of women and is usually a squamous carcinoma. Metastases are more common. Vaginal cancer occurs more often in women over age 50, but can occur at any age, even in...
, and penile cancer cases. HPV types 6 and 11 cause an estimated 90% of genital warts cases.
Gardasil has been used in prevention of two types of HPV infections, associated with approximately 70% of HPV cases. It does not treat existing infection. Therefore, to be effective it must be given before HPV infection occurs. The HPV strains that Gardasil protects against are sexually transmitted.
It was approved in the US on June 8, 2006 by the U.S. Food and Drug Administration (FDA). The FDA recommends vaccination before adolescence and potential sexual activity.
Development history
The research that led to the development of the vaccine began in the 1980s by groups at the University of RochesterUniversity of Rochester
The University of Rochester is a private, nonsectarian, research university in Rochester, New York, United States. The university grants undergraduate and graduate degrees, including doctoral and professional degrees. The university has six schools and various interdisciplinary programs.The...
, Georgetown University
Georgetown University
Georgetown University is a private, Jesuit, research university whose main campus is in the Georgetown neighborhood of Washington, D.C. Founded in 1789, it is the oldest Catholic university in the United States...
, and the US National Cancer Institute
National Cancer Institute
The National Cancer Institute is part of the National Institutes of Health , which is one of 11 agencies that are part of the U.S. Department of Health and Human Services. The NCI coordinates the U.S...
(NCI). In 1991, Australian investigators at The University of Queensland found a way to form non-infectious virus-like particles (VLP), which could also strongly activate the immune system. However, these VLPs assembled poorly and did not have the same structure as infectious HPV. In 1993, a laboratory at the US National Cancer Institute was able to generate HPV16 VLPs that were morphologically correct. These VLPs were the basis for the HPV16 component of the Gardasil vaccine. Upon commercialization of the vaccine, controversy involving intellectual property arose between the various groups that played a role in developing the vaccine.
Clinical trials
Merck & Co. conducted a Phase III study named Females United to Unilaterally Reduce Endo/Ectocervical Disease (FUTURE II). This clinical trial was a randomized double-blind study with one controlled placeboPlacebo
A placebo is a simulated or otherwise medically ineffectual treatment for a disease or other medical condition intended to deceive the recipient...
group and one vaccination group. Over 12,000 women aged 16–26 from thirteen countries participated in the study. Each woman was injected with either Gardasil or a placebo on day 1, month 2, and month 6. In total, 6,082 women were given Gardasil and 6,075 received the placebo. Subjects in the vaccine group had a significantly lower occurrence of high-grade cervical intraepithelial neoplasia related to HPV-16 or HPV-18 than did those in the placebo group. On February 27, 2006, the independent Data and Safety Monitoring Board recommended the clinical trials be terminated on ethical grounds, so that young women on placebo could receive Gardasil. Merck tested the vaccine in several hundred 11- and 12-year-old girls.
Indications and prevalence
Gardasil is a prophylactic HPV vaccine, meaning that it is designed to prevent HPV infections. For maximum effect, it is recommended that girls receive the vaccine prior to becoming sexually active. However, women who were already infected with one or more of the four HPV types targeted by the vaccine (6, 11, 16, or 18) were protected from clinical disease caused by the remaining HPV types in the vaccine.Since Gardasil will not block infection with all of the HPV types that can cause cervical cancer, the vaccine should not be considered a substitute for routine pap smear
Pap smear
The Papanicolaou test is a screening test used in to detect pre-cancerous and cancerous processes in the endocervical canal of the female reproductive system. Changes can be treated, thus preventing cervical cancer...
s.
Fewer HPV infections mean fewer complications from the virus and less time and money spent on the detection, work-up, and treatment of cervical cancer and its precursor, cervical dysplasia. It prevents infertility caused by cervical biopsies and reduces the severe respiratory problems of children who are infected by HPV from their mothers.
In addition, protection against HPV 6 and HPV 11 is expected to eliminate 90% of the cases of genital warts. Gardasil also protects against vulvar
Vulvar cancer
Vulvar cancer, a malignant invasive growth in the vulva, accounts for about 4 % of all gynecological cancers and typically affects women in later life. It is estimated that in the United States in 2006 about 3,740 new cases will be diagnosed and about 880 women will die as a result of vulvar cancer...
and vaginal cancer
Vaginal cancer
Vaginal cancer is any type of cancer that forms in the tissues of the vagina. Primary vaginal cancer is rare in the general population of women and is usually a squamous carcinoma. Metastases are more common. Vaginal cancer occurs more often in women over age 50, but can occur at any age, even in...
s caused by HPV types 16 and 18.
In December 2010, Gardasil was approved by the FDA for prevention of anal cancer and associated precancerous lesions due to human papillomavirus (HPV) types 6, 11, 16, and 18 in people ages 9 through 26 years.
HPV infections, especially HPV 16, contribute to some head and neck cancer
Head and neck cancer
Head and neck cancer refers to a group of biologically similar cancers that start in the upper aerodigestive tract, including the lip, oral cavity , nasal cavity , paranasal sinuses, pharynx, and larynx. 90% of head and neck cancers are squamous cell carcinomas , originating from the mucosal lining...
(HPV is found in an estimated 26-35% of head and neck squamous cell carcinoma). In principle, HPV vaccines may help reduce incidence of such cancers caused by HPV, but this has not been demonstrated.
Merck was denied FDA approval to market Gardasil to women aged 27 to 45. Although it was found to be safe and effective in the prevention of genital warts, it was not effective in the prevention of cervical cancer in that age group.
Use in males
Gardasil is also effective in males, providing protection against genital warts, anal cancerAnal cancer
Anal cancer is a type of cancer which arises from the anus, the distal orifice of the gastrointestinal tract. It is a distinct entity from the more common colorectal cancer. The etiology, risk factors, clinical progression, staging, and treatment are all different. Anal cancer is typically a...
, and some potentially precancerous lesions caused by some HPV types. An ongoing study of 4,065 males demonstrated the efficacy of Gardasil in males who did not have HPV infection prior to vaccination. The vaccination is expected to protect against penile cancer and anal cancer
Anal cancer
Anal cancer is a type of cancer which arises from the anus, the distal orifice of the gastrointestinal tract. It is a distinct entity from the more common colorectal cancer. The etiology, risk factors, clinical progression, staging, and treatment are all different. Anal cancer is typically a...
caused by included HPV types, and research in this area is still underway.
In December 2008, Merck asked the U.S. Food and Drug Administration (FDA) for permission to market the vaccine in the United States for males between ages 9 to 26, and the FDA approved the request on October 16, 2009. In the UK, HPV vaccines are already licensed for males aged 9 to 15 and for females aged 9 to 26.
Gardasil is in particular demand among gay men
Men who have sex with men
Men who have sex with men are male persons who engage in sexual activity with members of the same sex, regardless of how they identify themselves; many men choose not to accept sexual identities of homosexual or bisexual...
, who are at significantly increased risk for genital warts and anal cancer caused by HPV.
A 2005 study in San Francisco, California found that 95% of HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
-infected gay men also had anal HPV infection, of which 50% had precancerous HPV-caused lesions.
Type 16 is also associated with oropharyngeal squamous-cell carcinoma, a form of throat cancer.
Administration
Gardasil is given in three 0.5 milliliter injections over six months. The second injection is two months after the first, and the third injection is four months after the second shot was administered.Ingredients
- Proteins of HPV Types 6, 11, 16, and 18
- amorphous aluminum hydroxyphosphate sulfate (adjuvantAdjuvantAn adjuvant is a pharmacological or immunological agent that modifies the effect of other agents, such as a drug or vaccine, while having few if any direct effects when given by itself...
) - yeastYeastYeasts are eukaryotic micro-organisms classified in the kingdom Fungi, with 1,500 species currently described estimated to be only 1% of all fungal species. Most reproduce asexually by mitosis, and many do so by an asymmetric division process called budding...
protein - sodium chlorideSodium chlorideSodium chloride, also known as salt, common salt, table salt or halite, is an inorganic compound with the formula NaCl. Sodium chloride is the salt most responsible for the salinity of the ocean and of the extracellular fluid of many multicellular organisms...
- L-histidine
- polysorbate 80Polysorbate 80Polysorbate 80 is a nonionic surfactant and emulsifier derived from polyethoxylated sorbitan and oleic acid, and is often used in foods. Polysorbate 80 is a viscous, water-soluble yellow liquid...
- sodium borateBoraxBorax, also known as sodium borate, sodium tetraborate, or disodium tetraborate, is an important boron compound, a mineral, and a salt of boric acid. It is usually a white powder consisting of soft colorless crystals that dissolve easily in water.Borax has a wide variety of uses...
Biotechnology
The HPV major capsidCapsid
A capsid is the protein shell of a virus. It consists of several oligomeric structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or may not correspond to individual proteins, are called capsomeres. The capsid encloses the genetic...
protein, L1, can spontaneously self-assemble into virus-like particles (VLPs) that resemble authentic HPV virions. Gardasil contains recombinant
Recombinant virus
A recombinant virus is a virus produced by recombining pieces of DNA using recombinant DNA technology. This may be used to produce viral vaccines or gene therapy vectors....
VLPs assembled from the L1 proteins of HPV types 6, 11, 16 and 18. Since VLPs lack the viral DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
, they cannot induce cancer. They do, however, trigger an antibody
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
response that protects vaccine recipients from becoming infected with the HPV types represented in the vaccine. The L1 proteins are produced by separate fermentation
Ethanol fermentation
Ethanol fermentation, also referred to as alcoholic fermentation, is a biological process in which sugars such as glucose, fructose, and sucrose are converted into cellular energy and thereby produce ethanol and carbon dioxide as metabolic waste products...
s in recombinant Saccharomyces cerevisiae
Saccharomyces cerevisiae
Saccharomyces cerevisiae is a species of yeast. It is perhaps the most useful yeast, having been instrumental to baking and brewing since ancient times. It is believed that it was originally isolated from the skin of grapes...
and self-assembled into VLPs.
Efficacy
The National Cancer InstituteNational Cancer Institute
The National Cancer Institute is part of the National Institutes of Health , which is one of 11 agencies that are part of the U.S. Department of Health and Human Services. The NCI coordinates the U.S...
says, "Studies have shown that both Gardasil and Cervarix prevent nearly 100 percent of the precancerous cervical cell changes caused by the types of HPV targeted by the vaccine for up to 4 years after vaccination among women who were not infected at the time of vaccination."
Gardasil has been shown to be partially effective (approximately 38%) in preventing cervical cancer caused by ten other high-risk HPV types.
Safety
, 40 million doses of Gardasil had been distributed worldwide. The vaccine was tested in thousands of females (ages 9 to 26). The Food and Drug AdministrationFood and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
(FDA) and the Centers for Disease Control and Prevention
Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...
(CDC) consider the vaccine to be safe. It does not contain mercury
Mercury (element)
Mercury is a chemical element with the symbol Hg and atomic number 80. It is also known as quicksilver or hydrargyrum...
, thiomersal
Thiomersal
Thiomersal , and commonly known in the US as thimerosal, is an organomercury compound. This compound is a well established antiseptic and antifungal agent....
or live virus or dead virus, only virus-like particles, which cannot reproduce in the human body.
The FDA and the CDC say that the vaccine has only minor side effects, such as soreness around the injection area. Fainting is more common among adolescents receiving the Gardasil vaccine than in other kinds of vaccinations. Patients should remain seated for 15 minutes after they receive the HPV vaccine. There have been reports that the shot is more painful than other common vaccines, and the manufacturer Merck partly attributes this to the virus-like particles within the vaccine. General side effects of the shot may include joint and muscle pain, fatigue, physical weakness and general malaise.
An update on adverse events was published by the Journal of the American Medical Association
Journal of the American Medical Association
The Journal of the American Medical Association is a weekly, peer-reviewed, medical journal, published by the American Medical Association. Beginning in July 2011, the editor in chief will be Howard C. Bauchner, vice chairman of pediatrics at Boston University’s School of Medicine, replacing ...
and looked at data from the Vaccine Adverse Event Reporting System
Vaccine Adverse Event Reporting System
The Vaccine Adverse Event Reporting System is a United States program for vaccine safety, co-managed by the Centers for Disease Control and Prevention and the Food and Drug Administration . VAERS is a post-marketing safety surveillance program, collecting information about adverse events that...
(VAERS), covering 12,424 reported adverse events after about 23 million doses of vaccine between June 2006 and December 2008. Most adverse effects were minor and not greater than background rates compared with other vaccines, the exception being higher rates for syncope
Syncope (medicine)
Syncope , the medical term for fainting, is precisely defined as a transient loss of consciousness and postural tone characterized by rapid onset, short duration, and spontaneous recovery due to global cerebral hypoperfusion that most often results from hypotension.Many forms of syncope are...
and venous thromboembolic events. Venous thromboembolic events were noted in 56 reports at a rate of 0.2 cases per 100,000 doses distributed and included 19 cases of pulmonary embolism, four of which were fatal. Overall, 772 events (6.2% of the total number of adverse events, but only 0.003% of the total number of doses) were described as serious and included 32 deaths (1 per 1,000,000 doses).
Other adverse events include local site reactions (7.5 cases per 100,000 doses distributed), headaches (4.1 cases per 100,000 doses distributed), hypersensitivity reactions (3.1 cases per 100,000 doses distributed), and urticaria
Urticaria
Urticaria is a kind of skin rash notable for pale red, raised, itchy bumps. Hives is frequently caused by allergic reactions; however, there are many non-allergic causes...
(hives) (2.6 cases per 100,000 doses distributed).
The FDA and the CDC said that with millions of vaccinations "by chance alone some serious adverse effects and deaths" will occur in the time period following vaccination, but have nothing to do with the vaccine. More than 20 women who received the Gardasil vaccine have died, but these deaths have not been causally connected to the shot. Where information has been available, the cause of death was explained by other factors. Likewise, a small number of cases of Guillain-Barré Syndrome
Guillain-Barré syndrome
Guillain–Barré syndrome , sometimes called Landry's paralysis, is an acute inflammatory demyelinating polyneuropathy , a disorder affecting the peripheral nervous system. Ascending paralysis, weakness beginning in the feet and hands and migrating towards the trunk, is the most typical symptom...
(GBS) have been reported following vaccination with Gardasil, there is no evidence linking GBS to the vaccine. It is unknown why a person contracts GBS, or what initiates the disease.
The FDA and the CDC monitor events to see if there are patterns, or more serious events than would be expected from chance alone. The majority (68%) of side effects data were reported by the manufacturer, but in about 90% of the manufacturer reported events, no follow-up information was given that would be useful to investigate the event further. In February 2009, the Spanish ministry of health suspended use of one batch of Gardasil after health authorities in the Valencia region reported that two girls had become ill after receiving the injection. Merck has stated that there was no evidence Gardasil was responsible for the two illnesses.
Public health advantages
The National Cancer InstituteNational Cancer Institute
The National Cancer Institute is part of the National Institutes of Health , which is one of 11 agencies that are part of the U.S. Department of Health and Human Services. The NCI coordinates the U.S...
writes:
- Widespread vaccination has the potential to reduce cervical cancer deaths around the world by as much as two-thirds, if all women were to take the vaccine and if protection turns out to be long-term. In addition, the vaccines can reduce the need for medical care, biopsies, and invasive procedures associated with the follow-up from abnormal Pap tests, thus helping to reduce health care costs and anxieties related to abnormal Pap tests and follow-up procedures.
Long-term impact and cost-effectiveness
One unknown property of the vaccines now being researched is the persistence of their protective effects. Since the Gardasil vaccine has been administered for only a few years now, it is unknown whether it will provide life-long immunity to recipients. In coming decades, further study will answer this question.Whether the effects are temporary or life-long, widespread vaccination could have a substantial public health impact. 270,000 women died of cervical cancer worldwide in 2002. Acting FDA Administrator Dr. Andrew von Eschenbach
Andrew von Eschenbach
Andrew C. von Eschenbach was the Commissioner of the United States Food and Drug Administration from 2006–2009. He became acting Commissioner on September 26, 2005, after the resignation of his predecessor Lester Crawford, and was confirmed as Commissioner by the Senate on December 7, 2006...
said the
vaccine will have "a dramatic effect" on the health of women around the world. Even in the United States, where screening programs are routine, the National Cancer Institute
National Cancer Institute
The National Cancer Institute is part of the National Institutes of Health , which is one of 11 agencies that are part of the U.S. Department of Health and Human Services. The NCI coordinates the U.S...
estimated that 9,700 women would develop cervical cancer in 2006, and 3,700 would die.
Merck and CSL Limited
CSL Limited
CSL Limited is a global specialty biopharmaceutical company that researches, develops, manufactures and markets products to treat and prevent serious human medical conditions...
are expected to market Gardasil as a cancer vaccine, rather than an STD
Sexually transmitted disease
Sexually transmitted disease , also known as a sexually transmitted infection or venereal disease , is an illness that has a significant probability of transmission between humans by means of human sexual behavior, including vaginal intercourse, oral sex, and anal sex...
vaccine. It remains unclear how widespread the use of the three-shot series will be, in part because of its $360 list price ($120 each for three shots).
Since both men and women are carriers of HPV, vaccination of males could provide greater herd immunity
Herd immunity
Herd immunity describes a form of immunity that occurs when the vaccination of a significant portion of a population provides a measure of protection for individuals who have not developed immunity...
.
Studies using different pharmacoeconomic models predict that vaccinating young women with Gardasil in combination with screening programs may be more cost effective than screening alone. These results have been important in decisions by many countries to start vaccination programs. For example, the Canadian government approved $300 million to buy the HPV vaccine in 2008 after deciding from studies that the vaccine would be cost-effective especially by immunizing young women. Marc Steben, an investigator for the vaccine, wrote that the financial burden of HPV related cancers on the Canadian people was already $300 million per year in 2005, so the vaccine could reduce this burden and be cost-effective.
Since penile and anal cancers are much less common than cervical cancer, HPV vaccination of young men is likely to be much less cost-effective than for young women.
Diane Harper, one of the lead researchers for Gardasil, has called for more complete warnings for parents and questions its risk-versus-benefit profile because it is not yet known how long the vaccine will be effective once administered. The August 2009 issue of the Journal of the American Medical Association
Journal of the American Medical Association
The Journal of the American Medical Association is a weekly, peer-reviewed, medical journal, published by the American Medical Association. Beginning in July 2011, the editor in chief will be Howard C. Bauchner, vice chairman of pediatrics at Boston University’s School of Medicine, replacing ...
had an article reiterating the safety of Gardasil and another questioning the way it was presented to doctors and parents.
The new vaccine against 4 types of human papillomavirus (HPV), Gardasil, like other immunizations appears to be a cost-effective intervention with the potential to enhance both adolescent health and the quality of their adult lives. However, the messages and the methods by which the vaccine was marketed present important challenges to physician practice and medical professionalism. By making the vaccine's target disease cervical cancer, the sexual transmission of HPV was minimized, the threat of cervical cancer to adolescents was maximized, and the subpopulations most at risk practically ignored. The vaccine manufacturer also provided educational grants to professional medical associations (PMAs) concerned with adolescent and women's health and oncology. The funding encouraged many PMAs to create educational programs and product-specific speakers' bureaus to promote vaccine use. However, much of the material did not address the full complexity of the issues surrounding the vaccine and did not provide balanced recommendations on risks and benefits. As important and appropriate as it is for PMAs to advocate for vaccination as a public good, their recommendations must be consistent with appropriate and cost-effective use.
In an address at the 4th International Public Conference on Vaccination sponsored by the anti-vaccination group the National Vaccine Information Center
National Vaccine Information Center
The National Vaccine Information Center is a private non-profit 501 advocacy group which questions the safety and efficacy of commonly used vaccines. The group was founded in 1982 by parents who blamed routine vaccination for the illness or death of a child...
in October 2009, Dr. Diane Harper stated that in countries where Pap smear screening is common, it will take vaccination of a large proportion of women in order to further reduce cervical cancer rates. She also stated that no efficacy trials for children under 15 have been performed.
Political and other controversy
Medical groups, politicians and parents began rebelling after disclosure of a behind-the-scenes lobbying campaign by Gardasil's maker, Merck & Co., to get state legislatures to require 11- and 12-year-old girls to get the three-dose vaccine as a requirement for school attendance.Objections from doctors and parents groups were due to the vaccine protecting against a sexually transmitted disease, human papilloma virus, which causes cervical cancer. They cited that vaccines mandated are typically for diseases spread through casual contact, such as measles and mumps.
On February 20, 2007, Merck announced its immediate suspension of this campaign, which had been funded through a third party.
The governor of Texas, Rick Perry
Rick Perry
James Richard "Rick" Perry is the 47th and current Governor of Texas. A Republican, Perry was elected Lieutenant Governor of Texas in 1998 and assumed the governorship in December 2000 when then-governor George W. Bush resigned to become President of the United States. Perry was elected to full...
, issued an executive order adding Gardasil to the state's required vaccination list which was later overturned by the Texas legislature. Perry has also allowed parents to more easily opt-out of the program. Through lobbying efforts, Merck has suggested that governments make vaccination with Gardasil mandatory for school attendance, which has upset some conservative groups and libertarian groups. Conservative groups, including the Family Research Council
Family Research Council
The Family Research Council is a conservative or right-wing Christian group and lobbying organization formed in the United States in 1981 by James Dobson. It was fully incorporated in 1983...
(FRC), have expressed fear that vaccination with Gardasil might give girls a false sense of security regarding sex and lead to promiscuity.
During the Republican Party presidential debate
Republican Party (United States) presidential debates, 2012
The 2012 United States Republican Party presidential debates are a series of political debates being held, prior to the 2012 Republican primaries, among candidates for the Republican presidential nomination in the national election of 2012...
on September 12, 2011, candidates Congressman Ron Paul
Ron Paul
Ronald Ernest "Ron" Paul is an American physician, author and United States Congressman who is seeking to be the Republican Party candidate in the 2012 presidential election. Paul represents Texas's 14th congressional district, which covers an area south and southwest of Houston that includes...
and Representative Michele Bachmann
Michele Bachmann
Michele Marie Bachmann is a Republican member of the United States House of Representatives, representing , a post she has held since 2007. The district includes several of the northern suburbs of the Twin Cities, such as Woodbury, and Blaine as well as Stillwater and St. Cloud.She is currently a...
criticized fellow candidate Governor Rick Perry
Rick Perry
James Richard "Rick" Perry is the 47th and current Governor of Texas. A Republican, Perry was elected Lieutenant Governor of Texas in 1998 and assumed the governorship in December 2000 when then-governor George W. Bush resigned to become President of the United States. Perry was elected to full...
for his executive order. The following day, on the NBC Today Show Bachmann said “I will tell you that I had a mother last night come up to me here in Tampa, Fla., after the debate and tell me that her little daughter took that vaccine, that injection, and she suffered from mental retardation
Mental retardation
Mental retardation is a generalized disorder appearing before adulthood, characterized by significantly impaired cognitive functioning and deficits in two or more adaptive behaviors...
thereafter". In response, Merck rejected claims that Gardasil causes mental retardation and stated this side effect has never been reported for this vaccine. The comment may have resulted from confusion over the thimerosal controversy, in which similar claims have been made for other vaccines, but Gardasil does not contain thimerosal.
External links
- Silgard EPAR summary for the public
- Product Approval Information U.S. Food and Drug Administration (FDA)